Diols unsymmetrical

The pinacol rearrangement is frequently observed when geminal diols react with acid. The stmcture of the products from unsymmetrical diols can be predicted on the basis of ease of carbocation formation. For example, l,l-diphenyl-2-metltyl-l,2-propanediol rearranges to... 

Unsymmetrical diols typically give a mixture of pinacol products. For example, the diol shown below might give eight distinct products (counting cis and tmns diastereomers as distinct products). In fact, it gives only the two shown. 

In a study of stereochemistry, the half ether (5) of an unsymmetrical diol (6) was required. There is little prospect of making (5) from (6) as chemoselectlvity presents a formidable problem. Grignard disconnection from the tertiary alcohol would leave o-methoxyl ketones (7) or (8). 

Unsymmetrical vicinal diols can be prepared from a three-component reaction of aldehydes, CO, and aminotroponiminate-ligated titanium dialkyl complexes. Solutions of Me2TiL,2 (L = N -dimethylaminolroponiminalc) react rapidly with CO at room temperature. Double methyl migration to CO produces an 2-acclonc complex which inserts the aldehyde to afford a titana-dioxolane and releases the unsymmetrical diol upon hydrolysis [65]. 

Both unsymmetrical diols and alkenes can be prepared by applying these methods to mixtures of two different carbonyl compounds. An excess of one component can be used to achieve a high conversion of the more valuable reactant. A mixed reductive deoxygenation using TiCl4/Zn has been used to prepare 4-hydroxytamoxifen, the active antiestrogenic metabolite of tamoxifen. 

The synthetic protocols used for the preparation of oligonucleotides on supports can also be used to prepare oligomers from diols other than nucleosides. Symmetric or unsymmetric diols, such as N-acylated 4-hydroxyprolinol [268] or cyclopentane-derived diols (carbocyclic deoxyribose analogs [269]), can be selectively mono-trity-lated and then converted into a phosphoramidite that is suitable for the solid-phase synthesis of oligophosphates. An illustrative synthesis of protected //-phosphonates from diols, as well as their conversion on CPG into oligomeric phosphoramidates, are outlined in Figure 16.28. 

Regioselective oxidation of 1,2-diols.1 The oxidation of di-secondary glycols to acyloins (5, 188) can be extended to oxidation of other glycols. Thus the stan-nylene of 1 is oxidized by bromine to 2 in high yield. The reaction is regioselective with unsymmetrical diols (3 — 4). 

Stereochemical information on the mode of cyclodehydration of unsymmetrical diols to cyclic ethers could obviously have important consequences regarding useful, preparative routes to chiral cyclic ethers of high enantiomeric purity. For example, dioxyphos-phorane promoted cyclodehydration of a chiral diol can, in principle, give the enantiomeric ethers by either of two stereochemi-cally distinct routes. Separate stepwise decomposition of oxy-phosphonium betaines, A and B, although proceeded by a number of equilibria could ultimately afford a nonracemic mixture of cyclic ethers. 

Most unsymmetrical diols or epoxides give mixtures of products upon rearrangement. The problem is that there is a choice of two leaving groups and two alternative rearrangement directions, and only for certain substitution patterns is the choice clear-cut. 

Cleavage of acetals.1 In the presence of a Pd(II) catalyst, f-butyl hydroperoxide oxidatively cleaves a five- or six-membered acetal to an ester of a diol. Pd(OAc)2 and PdCl2 can catalyze this reaction, but CF3C02Pd00C(CH3)3 (10, 299) is most effective. The cleavage of acetals derived from unsymmetrical diols is not regioselective. 

The oxidation of primary alcohols to the corresponding carboxylic acid or ester generally requires fairly powerful oxidants, and in most cases the issue of selectivity is dealt with by protection of other oxidiz-able functionality within the molecule. One important area in which this need not be the case is the oxidation of symmetrical and unsymmetrical diols to the corresponding lactone. The general scheme is presented in Scheme S, and relies on an initial chemoselective oxidation to the hydroxy aldehyde, which is in equilibrium with the lactol. This lactol is then oxidized to the lactone. In some cases it is possible to halt the reaction at the lactol stage, but usually the lactone is the product. Most of this section will be concerned with this type of selective oxidation. 

Results which follow the mechanistic generalizations given above have been obtained from examination of similar unsymmetrical diols. The formation of (24) as the major product from (23) can be explained by more rapid development of the carbenium ion in the five-membered ring (equation 15). 

Other unsymmetrical diols, prepared (inefficiently) by the coupling of mixtures of ketones, have been studied. The preferred cation argument is also found to be applicable to mixed medium-ring analogs, i.e. the kinetically favored pinacol rearrangement product is that predicted by consideration of the relative stabilities of the two possible, initially formed, carbocations. ° Earlier work with these compounds may have given misleading results due to product instability. To illustrate, Mundy observed that (24) is converted to (25) as the temperature is increased. 

These results are consistent with a model for the reaction in which adsorption of an unsymmetrical diol to the surface of AI2O3 occurs primarily via the least hindered hydroxyl group. Interaction of the adsorbed hydroxyl group with the surface effectively shields that site leaving only the non-adsorbed group available for reaction with the added acetylating agent. 

Unsymmetrical diols provide a serious problem of chemoselectivity with an ingenious solution.7 Treatment of the diol 49 with acid leads to loss of OH from what would be the more stable /-alkyl cation and hence, by hydrogen shift, to the ketone 51. 

Allylation of acylsilanes and a-ketoesters proceeds normally. Monoallylation of a-diketones is also easily realized, whereas glyoxal A7Ai-monohydrazone gives 1,7-octa-diene-4,5-diol. However, sequential reactions of the glyoxal monohydrazone with RLi and then allylindium reagent lead to unsymmetrical diols. ... 

If there is a good leaving group at the 2- or 3-position, then ring closure, via C—C bond formation, is afforded by internal nucleophilic displacement of the kind shown in equation 25. The best leaving groups appear to be sulphonates, but halogens can also be displaced as shown by the formation of the y-sultone 13 in equation 26. In accord with the mechanism already discussed, dimethyl sulphonate esters of unsymmetrical diols such as... 

In one of the first significant modifications of the Watanabe ruthenium catalyst for indolization, Zhang, Ding, and coworkers used [Ru(CO)jXantphos]j (1) to synthesize indoles from anilines and vicinal symmetrical and unsymmetrical diols both (Scheme 4) [26]. Madsen and his colleagues employed a RuCyphosphine catalyst to prepare 2,3-disubstituted indoles from anilines and 1,2-diols, and they also found that a [Cp IrCl2l2/MsOH catalyst is equally effective in this reaction [27], Iridium-based... 

The reaction occurs in an exclusively intramolecular fashion. As such, symmetrical diols will yield a single product, while unsymmetrical diols may lead to product mixtures. 

Using an unsymmetrical diol had an adverse effect on light-transmittance characteristics, perhaps because such diols have poor molecular structural fit, allowing the growth of local crystallites which cause opacity. Examples of such systems are T4, TIO, T12, T13, T14, T15 and T9 in Table 12.4. 

Scheme 4.24 DKRs of unsymmetrical diols with Shvo s catalyst.

---